Home > Research > Publications & Outputs > A bivariate Bayesian dose-finding procedure app...

Research

Associated organisational units

Links

Text available via DOI:

Keywords

View graph of relations

A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis. / Thygesen, Helene; Dragalin, Vlad; Whitehead, Anne et al.
In: Pharmaceutical Statistics, Vol. 11, No. 6, 11.2012, p. 476-484.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Thygesen, H, Dragalin, V, Whitehead, A & Whitehead, J 2012, 'A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis', Pharmaceutical Statistics, vol. 11, no. 6, pp. 476-484. https://doi.org/10.1002/pst.1539

APA

Thygesen, H., Dragalin, V., Whitehead, A., & Whitehead, J. (2012). A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis. Pharmaceutical Statistics, 11(6), 476-484. https://doi.org/10.1002/pst.1539

Vancouver

Thygesen H, Dragalin V, Whitehead A, Whitehead J. A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis. Pharmaceutical Statistics. 2012 Nov;11(6):476-484. Epub 2012 Sept 25. doi: 10.1002/pst.1539

Author

Thygesen, Helene ; Dragalin, Vlad ; Whitehead, Anne et al. / A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis. In: Pharmaceutical Statistics. 2012 ; Vol. 11, No. 6. pp. 476-484.

Bibtex

@article{6ac2e1e5ad014157846efbc8e30f4d74,
title = "A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis",
abstract = "We describe a dose escalation procedure for a combined phase I/II clinical trial. The procedure is based on a Bayesian model for the joint distribution of the occurrence of a dose limiting event and of some indicator of efficacy (both considered binary variables) making no assumptions other than monotonicity. Thus the chances of each outcome are assumed to be nondecreasing in dose level. We applied the procedure to the design of a placebo-controlled, sequential trial in rheumatoid arthritis, in each stage of which patients were randomized between placebo and all dose levels that currently appeared safe and non-futile. Based on data from a pilot study, we constructed five different scenarios for the dose-response relationships under which we simulated the trial and assessed the performance of the procedure. The new design appears to have satisfactory operating characteristics, and can be adapted to the requirements of a range of trial situations.",
keywords = "dose finding, bivariate outcome, phase I/II trial, Bayesian methods, safety monitoring, futility",
author = "Helene Thygesen and Vlad Dragalin and Anne Whitehead and John Whitehead",
year = "2012",
month = nov,
doi = "10.1002/pst.1539",
language = "English",
volume = "11",
pages = "476--484",
journal = "Pharmaceutical Statistics",
issn = "1539-1604",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

RIS

TY - JOUR

T1 - A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis

AU - Thygesen, Helene

AU - Dragalin, Vlad

AU - Whitehead, Anne

AU - Whitehead, John

PY - 2012/11

Y1 - 2012/11

N2 - We describe a dose escalation procedure for a combined phase I/II clinical trial. The procedure is based on a Bayesian model for the joint distribution of the occurrence of a dose limiting event and of some indicator of efficacy (both considered binary variables) making no assumptions other than monotonicity. Thus the chances of each outcome are assumed to be nondecreasing in dose level. We applied the procedure to the design of a placebo-controlled, sequential trial in rheumatoid arthritis, in each stage of which patients were randomized between placebo and all dose levels that currently appeared safe and non-futile. Based on data from a pilot study, we constructed five different scenarios for the dose-response relationships under which we simulated the trial and assessed the performance of the procedure. The new design appears to have satisfactory operating characteristics, and can be adapted to the requirements of a range of trial situations.

AB - We describe a dose escalation procedure for a combined phase I/II clinical trial. The procedure is based on a Bayesian model for the joint distribution of the occurrence of a dose limiting event and of some indicator of efficacy (both considered binary variables) making no assumptions other than monotonicity. Thus the chances of each outcome are assumed to be nondecreasing in dose level. We applied the procedure to the design of a placebo-controlled, sequential trial in rheumatoid arthritis, in each stage of which patients were randomized between placebo and all dose levels that currently appeared safe and non-futile. Based on data from a pilot study, we constructed five different scenarios for the dose-response relationships under which we simulated the trial and assessed the performance of the procedure. The new design appears to have satisfactory operating characteristics, and can be adapted to the requirements of a range of trial situations.

KW - dose finding

KW - bivariate outcome

KW - phase I/II trial

KW - Bayesian methods

KW - safety monitoring

KW - futility

U2 - 10.1002/pst.1539

DO - 10.1002/pst.1539

M3 - Journal article

VL - 11

SP - 476

EP - 484

JO - Pharmaceutical Statistics

JF - Pharmaceutical Statistics

SN - 1539-1604

IS - 6

ER -